Diagram depicting antibiotic resistance through alteration of the antibiotic’s target site, modeled after MRSA’s resistance to penicillin. Beta-lactam antibiotics permanently inactivate PBP enzymes, which are essential for bacterial life, by permanently binding to their active sites. MRSA, however, expresses a PBP that will not allow the antibiotic into its active site. (Photo credit: Wikipedia)
The fight against antibiotic-resistant superbugs has taken a step forward thanks to a new discovery by scientists at The University of Nottingham.
A multi-disciplinary research team at the University’s Centre for Biomolecular Sciences has uncovered a new way of inhibiting the toxicity and virulence of the notorious superbug, Pseudomonas aeruginosa.
This bacteria produces an armoury of virulence factors and is resistant to many conventional antibiotics. It is almost impossible to eradicate P. aeruginosa from the lungs of people with cystic fibrosis and is therefore a leading cause of death among sufferers. The bug also causes a wide range of infections particularly among hospital patients.
The new discovery concerns the bacterial cells’ ability to ‘talk’ to each other by producing and sensing small chemical signal molecules. This is called ‘quorum sensing’ (QS) and enables a population of individual bacteria to act socially rather than as individuals. QS allows a population of bacteria to assess their numerical strength and make a decision only when the population is ‘quorate’.
The mechanism through which QS signals work is by activating gene expression upon interaction of a QS signal molecule with a receptor protein. In many disease-causing bacteria, QS controls genes which are essential for infection. These genes code for virulence factors such as toxins which cause damage to host tissues and the immune system. Interfering with the QS signalling process blocks bacterial virulence and renders bacteria unable to cause infection. Consequently QS systems are molecular targets for the development of new anti-infective drugs which do not kill bacteria but instead block their ability to cause disease.
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